Structural highlights
3v6o is a 6 chain structure with sequence from Human and Mus musculus. The May 2012 RCSB PDB Molecule of the Month feature on Leptin by David Goodsell is 10.2210/rcsb_pdb/mom_2012_5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| Gene: | DB, LEPR, OBR (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[LEPR_HUMAN] Obesity due to leptin receptor gene deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
[LEPR_HUMAN] Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lymphopoiesis. May play a role in reproduction. Can also mediate the ERK/FOS signaling pathway (By similarity).
Publication Abstract from PubMed
Leptin regulates energy homeostasis, fertility, and the immune system, making it an important drug target. However, due to a complete lack of structural data for the obesity receptor (ObR), leptin's mechanism of receptor activation remains poorly understood. We have crystallized the Fab fragment of a leptin-blocking monoclonal antibody (9F8), both in its uncomplexed state and bound to the leptin-binding domain (LBD) of human ObR. We describe the structure of the LBD-9F8 Fab complex and the conformational changes in 9F8 associated with LBD binding. A molecular model of the putative leptin-LBD complex reveals that 9F8 Fab blocks leptin binding through only a small (10%) overlap in their binding sites, and that leptin binding is likely to involve an induced fit mechanism. This crystal structure of the leptin-binding domain of the obesity receptor will facilitate the design of therapeutics to modulate leptin signaling.
Structure of the human obesity receptor leptin-binding domain reveals the mechanism of leptin antagonism by a monoclonal antibody.,Carpenter B, Hemsworth GR, Wu Z, Maamra M, Strasburger CJ, Ross RJ, Artymiuk PJ Structure. 2012 Mar 7;20(3):487-97. PMID:22405007[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Carpenter B, Hemsworth GR, Wu Z, Maamra M, Strasburger CJ, Ross RJ, Artymiuk PJ. Structure of the human obesity receptor leptin-binding domain reveals the mechanism of leptin antagonism by a monoclonal antibody. Structure. 2012 Mar 7;20(3):487-97. PMID:22405007 doi:10.1016/j.str.2012.01.019
